A 28-year-old man presents with palpitations, tremor, and weight loss despite good appetite for 2 weeks. Heart rate is 110 bpm, and he appears anxious. Serum TSH is suppressed at 0.05 mIU/L (normal 0.4–4.0). Which investigation is most appropriate to confirm thyroid hormone excess and differentiate the cause?

## Investigation Strategy in Suspected Hyperthyroidism ### Clinical Context The patient presents with classic hyperthyroid symptoms (palpitations, tremor, weight loss, anxiety, tachycardia) and has a suppressed TSH. The next step is to confirm thyroid hormone excess by measuring free T3 and free T4. ### Why Free T3 and Free T4 are the Investigations of Choice **Key Point:** A suppressed TSH alone does not confirm hyperthyroidism—it must be accompanied by elevated free T3 and/or free T4. Both are measured because: 1. **T3-toxicosis:** Some patients (especially early Graves' disease) have elevated T3 with normal T4 2. **T4-toxicosis:** Others have isolated elevated T4 3. **Combined elevation:** Most common in overt hyperthyroidism **High-Yield:** The diagnostic algorithm is: 1. Suppressed TSH → measure free T3 *and* free T4 2. If both elevated → hyperthyroidism confirmed 3. If only T3 elevated → T3-toxicosis (often early Graves' disease) ### Diagnostic Confirmation | Investigation | Role in Hyperthyroidism | | --- | --- | | Free T3 + Free T4 | Confirms thyroid hormone excess; detects T3-toxicosis | | TSH | Suppressed; non-specific (also suppressed in secondary/tertiary hyperthyroidism) | | TPO antibodies | Present in Hashitoxicosis; not specific for Graves' disease | | TSI (TRAb) | Specific for Graves' disease; used *after* diagnosis confirmed | | Thyroid uptake scan | Differentiates etiology (high in Graves', low in thyroiditis); not for initial confirmation | **Clinical Pearl:** Free T3 and T4 (not total) are preferred because they are unaffected by thyroid-binding globulin and reflect biologically active hormone. ### Role of Other Investigations - **TSI/TRAb assay:** Specific for Graves' disease but is a secondary investigation used to determine *etiology* after hyperthyroidism is confirmed. Not needed for initial diagnosis. - **TPO antibodies:** May be positive in autoimmune thyroid disease but lack specificity for Graves' disease. - **Thyroid uptake scan:** Excellent for differentiating etiology (high uptake in Graves', low in thyroiditis) but is not the first confirmatory test. Usually performed after biochemical confirmation.